This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We recently reported high levels of virus replication, acute CD4+ T cell depletion in the gut associated lymphoid tissues (GALT), and coreceptor switch in Indian (Ind) RMs infected intravenously (IV) with the late R5 tropic SHIVSF162P3N isolate. To more closely mimic the common modes of transmission of HIV-1 in humans, infection though the rectal route of SHIVSF162P3N was examined. In Preliminary studies, we show that mucosal infection of Ind RMs with R5 SHIVSF162P3N recapitulates key pathogenic features of HIV-1 infection in humans including acute CD4+ T cell depletion in the gut, uncontrolled replication, and progression to AIDS with switch in coreceptor preference. The consistency of high setpoint viremia and pathogenicity seen in SHIVSF162P3N IV and IR infected macaques leads us to hypothesize that this animal model system will be highly relevant not only for in-depth studies of the evolutionary process and the underlying mechanism for the change in coreceptor preference in vivo, but also for advancing the discovery of HIV-1 candidate vaccines that stimulate both effector arms of the immune system.